Abstract This application requests the fourth renewal of our Chemistry-Biology Interface (CBI) Training Grant. In 1995 we launched a new interdisciplinary training program at the University of Massachusetts that built on existing strengths and harnessed our faculty commitment to collaboration between the physical and life sciences. We successfully implemented a curriculum that complemented the requirements of the participating graduate programs, adding enough training elements to efficiently train students with either chemical or biological backgrounds in the complementary discipline. The subsequent period (2000-2005) was one of tremendous growth: the number of CBI Program Members grew from 14 to over 60, as students well beyond those with CBI funding recognized the value of the training and community. Since then the program has continued to thrive, with membership remaining strong at 66 in 2010 and 72 CBI Program Members today. The success of the CBI program in establishing a collaborative community and interdisciplinary curriculum has led to major expansion of this research area on campus. In the current funding period we have seen significant investment by the university and the state in infrastructure and equipment, and the creation of a new Institute for Applied Life Sciences that connects many of the strong CBI research clusters with other life science researchers and engineers across campus. The 27 CBI Training Faculty continue to provide cross- training to over 70 students from the four participating graduate programs of Chemistry, Molecular & Cellular Biology, Chemical Engineering, and Polymer Science & Engineering. The CBI Program currently provides NIH support for 7 pre-doctoral students (reduced from 8 approved slots by NIH budget constraints), and a University match supports 2 additional Traineeships. Our inclusive approach combined with this university match has expanded training benefits 10-fold (7 NIH traineeships seed CBI training of 72 CBI Members). In view of the recent expansion of high TGE CBI Program Members from 35 in 2010 to 52 in 2015, we request an increase to 9 NIH-funded Traineeships. Central features of the CBI Program include the well-attended community-building Chalk Talk series, the popular Drug Design course featuring speakers from pharmaceutical companies, and an annual Retreat that forges connections with researchers at UMass Medical School. New training initiatives for the next funding period include a required Reproducibility in Research module, an optional computational drug discovery workshop and course, a CBI Toolbox Tour element of Chalk Talk to stimulate training and discussion of our significantly expanded instrumentation capabilities, and an increase to four CBI student-invited seminars to build even stronger community ties to all four participating programs. Thus the CBI curriculum and community are rich in opportunities for training in the methods and intellectual framework of both chemistry and biology, which prepares our CBI graduates to pose and solve significant biomedical questions in their future work.